The ability to produce defined changes in individual genes through transgenic and gene knockout technologies has provided investigators with powerful tools for understanding the role of specific genes and their corresponding proteins in a variety of biological processes and with the ability to monitor changes in genomic integrity in virtually every cell and tissue type, including post mitotic tissues. Sophisticated methods of regulating gene expression with molecular switches (e.g., tetracycline binary system of gene regulation, Cre recombinase-mediated regulation of sequences flanked by lox P sites) combined with transgenic and gene knockout technologies are facilitating investigations into the roles of specific genes in aging in adult animals by bypassing embryonic expression. Most recently, RNAi has been shown to be a powerful method for studying the role of specific genes and their corresponding proteins and can be used in conjunction with transgenic technology to produce animals in which reduced abundance of specific proteins can be achieved. These genetic manipulations can be used with traditional methods of studying aging (e.g., lifespan studies, cross-sectional pathology studies) to test directly the role of specific genes in aging. The major function of the Transgenic Core is to make genetically manipulated rodents for aging studies. This Core is essential for investigators interested in studying the roles of specific genes in aging and age-related diseases. Accordingly, the Specific Aims of the Transgenic Core are: 1. To produce and identify transgenic founder mice and rats. 2. To assist investigators in the production of mice carrying gene knockouts. 3. To provide educational activities for students, postdoctoral fellows, investigators, and laboratory personnel engaged in using transgenic rodents. 4. To implement new technologies for generating genetically engineered rodents as the need arises.